The role of European genetic admixture in the etiology of the insulin resistance syndrome in children: are the effects mediated by fat accumulation?

OBJECTIVES: To evaluate the contribution of European genetic admixture (EUADM) to insulin resistance syndrome (IRS) in a multiethnic sample of children age 7-12 years, and to explore whether body fat affects this relationship. STUDY DESIGN: Anthropometric measurements and blood pressure were assessed in 243 children. After an overnight fast, an intravenous glucose tolerance test was conducted, and measures of fasting insulin/glucose, lipids, insulin sensitivity (SI), and acute insulin response to glucose (AIRg) were obtained. The proportion of EUADM was determined by maximum likelihood estimation using 140 ancestry informative markers. Subjects were stratified into tertiles according to the proportion of EUADM for analyses. Subjects were categorized as lean or obese using body fat percentage cutpoints (25% in boys, 30% in girls). RESULTS: Among lean subjects (72%), the tertile representing the greatest proportion of EUADM was associated with higher SI (P<.001) and serum glucose (P<.05) and lower insulin (P<.05), AIRg (P<.001), high-density lipoprotein cholesterol (P=.05), and blood pressure (P<.05). However, among obese subjects, EUADM was associated only with SI (P<.05). CONCLUSIONS: Our results suggest that population differences in IRS likely have a genetic component, but that the influence of genetic background may be masked by obesity.

IGF-I polymorphism is associated with lean mass, exercise economy, and exercise performance among premenopausal women.

BACKGROUND: We undertook this study to investigate the association of a genetic polymorphism of the insulin-like growth factor, IGF-I(189), on body composition, exercise performance and exercise economy, after controlling for the independent effect of race as assessed by African genetic admixture (AFADM). METHODS: A total of 114 premenopausal sedentary women were genotyped for IGF-I189, obtaining measures of fat mass, lean body mass, VO2 during cycling and stairclimbing, time on treadmill and leg strength. A quantitative value for AFADM was derived from genotypic information of approximately 40 ancestry informative markers and used as covariate in statistical models. RESULTS: After adjusting for AFADM, IGF-I189 was negatively associated with lean body mass (p = 0.029) and lean leg mass (p = 0.050). Leg strength was not associated with the presence/absence of IGF-I189 (p = 0.380), but carriers of the allele demonstrated a longer time on the treadmill (p = 0.015) after adjusting for AFADM. There was also a negative relationship between oxygen uptake during cycling and presence of the IGF-I189 independent of AFADM (p = 0.010). CONCLUSIONS: Independent of AFADM, individuals with IGF-I189 are more likely to have low leg lean mass and to perform better in activities requiring exercise economy and endurance performance.

Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty.

OBJECTIVE: To determine longitudinal changes in insulin sensitivity (SI), insulin secretion, and beta-cell function during puberty in white and black youth. STUDY DESIGN: The tolbutamide-modified frequently sampled intravenous glucose tolerance test and minimal modeling were used to measure SI, the acute insulin response to glucose (AIRg), and beta-cell function (disposition index, DI) in white (n = 46) and black (n = 46) children (mean [+/-SD] age at baseline = 10.2 +/- 1.7 years). Growth curve models (including 272 observations) with SI, AIRg, and DI regressed on Tanner stage were run after adjusting for covariates. RESULTS: After adjusting for covariates, growth curve models revealed that SI decreased and subsequently recovered by the end of puberty in whites and blacks (both p < .05), AIRg decreased linearly across Tanner stages in both races (both p < .001), and DI decreased across puberty in blacks (p = .001) but not in whites (p = .2). CONCLUSIONS: White and black youth exhibited transient insulin resistance and diminished AIRg during puberty. The progressive decline in DI among blacks versus whites may reflect a unique effect of puberty on beta-cell compensation in blacks. Future studies are needed to identify whether this difference contributes to the increased risk of type II diabetes in young blacks.

Ability of the actiwatch accelerometer to predict free-living energy expenditure in young children.

OBJECTIVE: To determine whether activity counts obtained with the Actiwatch monitor are associated with total expenditure and body composition in young children. RESEARCH METHODS AND PROCEDURES: Actiwatch activity monitors were tested in 29 children 4 to 6 years old under field conditions over eight days. Total energy expenditure (TEE) was assessed with the doubly labeled water (DLW) technique. Correlation analyses were used to identify variables related to energy expenditure and percentage body fat. Multiple linear regression analyses were used to examine the variance in TEE and percentage body fat explained by activity counts after adjusting for relevant covariates. RESULTS: Both average total daily activity counts (658,816 +/- 201,657) and the pattern of activity were highly variable among subjects. TEE was significantly related to lean body mass (r = 0.45) and age (r = 0.48; p < 0.05 for both). Activity counts alone were not associated with TEE. In multiple linear regression analyses, TEE was independently associated with only lean body mass. Percentage fat mass was independently associated with body weight, being a girl, and being white, but not with average total activity counts. DISCUSSION: Activity counts obtained with the Actiwatch under free-living conditions do not reflect TEE in 4- to 6-year-old children and are not correlated with percentage fat mass. Therefore, average total activity counts obtained with the Actiwatch may be of limited value in identifying children at risk for becoming obese.

Relations of fatness and fitness to fasting insulin in black and white adolescents.

OBJECTIVE: To determine in black and white youths the degree to which fatness and cardiovascular fitness (CVF) explained independent proportions of the variance in fasting insulin concentrations. STUDY DESIGN: Youths 14 to 18 years of age (n = 278) were studied. Insulin was measured after a 12-hour fast. Percent body fat (%BF) was measured with dual-energy x-ray absorptiometry. CVF was determined with a multistage treadmill test. RESULTS: Girls had higher %BF and lower CVF than boys. Whites were higher in CVF than blacks. There was a race by sex interaction for fasting insulin concentration, such that black girls had the highest and white girls had the lowest concentrations. When %BF and CVF was controlled statistically, this interaction was no longer significant. Multiple regression models that controlled for race, sex, and their interaction showed that (1) both higher %BF and lower CVF were significantly associated with higher insulin concentrations; (2) there were significant interactions with sex, such that the deleterious effects of low CVF and high %BF were greater in boys than in girls; (3) there was a significant CVF-%BF interaction, such that youths who were both fit and lean had especially low insulin concentrations; and (4) sex-specific regressions showed that both %BF and CVF explained significant independent proportion of the insulin variance for the boys but that only %BF did so for the girls. CONCLUSIONS: Interventions to prevent hyperinsulinemia in youths should be designed both to minimize fatness and maximize CVF.